# Advanced Characterization of Environmental Pollutant Metabolism in Human Skin

## TL;DR

This study uses advanced techniques to track how human skin processes a harmful pollutant, benzo[a]pyrene, revealing key metabolic products and improving understanding of pollution-related health risks.

## Contribution

A novel method combining stable isotope labeling and LC-HRMS is introduced for detailed analysis of BaP metabolism in human skin.

## Key findings

- Five distinct BaP phase I metabolites were identified in human skin models.
- The method enables comprehensive characterization of BaP metabolic pathways.
- The approach can be applied to study other environmental pollutants in human skin.

## Abstract

Ultrafine particles (UFPs) containing polycyclic aromatic hydrocarbons (PAHs) benzo[a]pyrene (BaP), are linked to pollution-induced health concerns, with skin being highly susceptible to contamination. Understanding the metabolic fate of these environmental pollutants in the skin is crucial. Moreover, traditional in vitro models often lack metabolic competency, while animal testing raises ethical concerns. This study introduces a novel approach combining stable isotope labeling (SIL) and liquid chromatography–high-resolution mass spectrometry (LC-HRMS) to investigate BaP metabolism. The physiologically relevant 3D reconstructed human epidermis (RHE) model was used. RHE models were exposed to BaP and deuterium-labeled BaP (BaP-d12). These analyses, followed by data analysis incorporating stable isotope filtering, revealed the presence of five distinct BaP phase I metabolites, including mono-hydroxylated, dihydroxylated, and quinone derivatives. This study demonstrates the power of coupling stable isotope labeling with LC-HRMS for the comprehensive characterization of BaP metabolic pathways in human skin. The identification of specific metabolites enhances our understanding of BaP detoxification mechanisms and their potential adverse effects. This analytical approach holds promise for investigating the metabolic fate of various other environmental pollutants.